Diabetes is a disorder of metabolism in which either the pancreas produces too little or no insulin, or the body cells do not respond to the insulin that is produced. In type I diabetes, the pancreas does not produce any insulin. In type II diabetes, also known as adult onset diabetes, there are two potential problems: the pancreas produces too little insulin, or the body cells do not respond to the insulin that is produced. In either scenario, the glucose cannot efficiently move from the blood to the cells, which leads to a buildup of glucose in the blood and an overflow into the urine. As a result, the body loses its main source of fuel. Administering insulin or oral antihyperglycemic agents allows the glucose to enter the cells more efficiently, thus providing a source of fuel.
Thiazolidinedione antihyperglycemics (benzylidenethiazolidinedione antihyperglycemics) are a class of drugs, useful in treating type II diabetes and other disorders relating to insulin resistance, that share a 5-(4-alkoxyphenyl)methyl-2,4-thiazolidinedione (I) pharmacophore. 
Pioglitazone is an oral thiazolidinedione antihyperglycemic agent that acts primarily by decreasing insulin resistance. Pharmacological studies indicate that pioglitazone improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Pioglitazone improves glucose resistance while reducing circulating insulin levels.
Pioglitazone, as its hydrochloride, is currently marketed as ACTOS®. Pioglitazone hydrochloride has the chemical name [(±)5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-] thiazolidinedione monohydrochloride. (CAS Registry No 111025-46-8). The chemical structure of pioglitazone is shown as structure II. 
U.S. Pat. No. 5,952,509, incorporated herein by reference, discloses methods for the synthesis of pioglitazone.
Rosiglitazone, 5-[4-[2-[N-methyl-N-(pyridin-2-yl)aminoethoxy]phenyl]methyl-2,4-thiazolidinedione, and troglitazone, 5-[4-[(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)methoxy]benzyl]-2,4-thiazolidinedione, are also a thiazolidinedione antihyperglycemics useful in treating type II diabetes and other disorders relating to insulin resistance. Rosiglitazone is marketed under the trade name Avandia®. Troglitazone has been marketed under the trade name Prelay®.
Methods for making pioglitazone, rosiglitazone, and troglitazone may proceed via a thiazolidinedione precursor having an exocyclic carbon-carbon double bond at the 5 position of a thiazolidinedione ring. The method of making pioglitazone disclosed in U.S. Pat. No. 5,952,509 is such a method. In such methods, the carbon-carbon double bond must be hydrogenated to a carbon-carbon single bond to form the thiazolidinedione antihyperglycemic. Catalytic hydrogenation over a supported catalyst, a method generally well known in the art, has been used to this end.
Synthesis of rosiglitazone via a thiazolidinedione precursor is disclosed in, for example, U.S. Pat. No. 5,002,953 (the '953 patent). Synthesis of troglitazone via a thiazolidinedione precursor is disclosed in J. Cossy et al., A Short Synthesis of Troglitazone: An Antidiabetic Drug for Treating Insulin Resistance, 9 Bioorganic and Medicinal Chemistry Letters, 3439-3440 (1999).
When the thiazolidinedione precursor is a solid, which is usually the case, a solvent must be used in the hydrogenation step. Hydrogenation of the thiazolidinedione pioglitazone precursors in solvents such as dioxane and particularly DMF has been reported. Large quantities (up to 20 volumes) of such solvents are required. When these solvents may be used, higher pressures (e.g. 50-100 atm) and a large amount of catalyst (ratio of weight of catalyst to weight of precursor of 1 to 3) are required. Even with such large amounts of catalyst, longer reaction times, e.g. ≧72 hr in some cases, are required to obtain only fair yields, e.g. 35-40%.